patient care perspectives

Depression, Inflammation, and Cardiometabolic Risk

by Charles F. Reynolds, III, MD

Overview

Studies on the link between depressive symptoms and cardiometabolic conditions have generated inconsistent findings. Since the symptoms of major depressive disorder (MDD) are notably heterogeneous, researchers recently sought to identify empirically derived “depressive symptom profiles” and link them to cardiometabolic outcomes. Latent profile analysis was used to identify 4 distinct depressive symptom profiles. These 4 symptom profiles were then analyzed for their associated cardiometabolic outcomes and the relationship to inflammation. Investigators found that inflammation attenuated the association between depressive subgroups and cardiometabolic outcomes, suggesting that inflammation may be a biological mediator of such outcomes.

Expert Commentary

Charles F. Reynolds, III, MD

Distinguished Professor of Psychiatry Emeritus
University of Pittsburgh
School of Medicine
Pittsburgh, PA

“We’ve gotten very interested in the proinflammatory cytokine activity that we see in depression. Our colleague at UT Houston is investigating the role of proinflammatory cytokine activity in older adults with depression and how that may signal the rate of cognitive decline.”

Charles F. Reynolds III, MD

A leading hypothesis is that inflammation serves as a biological pathway linking depression to cardiometabolic risk. Indeed, proinflammatory activity is of interest for a variety of reasons. We’ve gotten very interested in the proinflammatory cytokine activity that we see in depression. Our colleague at UT Houston is investigating the role of proinflammatory cytokine activity in older adults with depression and how that may signal the rate of cognitive decline.

Studies examining the link between depressive symptoms and cardiometabolic conditions, however, have yielded inconsistent results. A recently published study by Chirinos et al takes aim at some of these areas of inconsistency to try to help fill this gap. Findings were published in the August 2017 issue of Psychoneuroendocrinology.

Investigators developed an analytic approach using several “depressive symptom profiles” and the inflammatory biomarker, C-reactive protein (CRP), in participants enrolled in the MIDUS (Midlife in the Unites States) study. Their sample is composed of a subset from the second wave of this study, the MIDUS-II study, with a total of 1255 individuals who had completed the study’s biomarker project.

As backdrop to their analysis, the authors noted previous work by Shelton and Miller and by others who have contributed to the “inflammatory hypothesis” of depression.

 

Cardiometabolic Risk_Inflammation

 

The authors noted several recent developments in regard to links between depressive symptoms and metabolic syndrome:

  • In a recent meta-analysis, there was a stronger association between metabolic syndrome and depression when measured by self-reported scales rather than a structured clinical interview or clinical diagnosis; self-report scales may help characterize profiles as they provide valuable information on the nature of symptoms (eg, cognitive vs somatic) as well as their severity (eg, higher scores characteristic of more severe depression).
  • In another recent study, depressive symptoms were associated with 1.17-1.25 increased odds of metabolic syndrome incidence after 15 years, suggesting they may predict the development of cardiometabolic conditions, even at subclinical levels.

In the present study, the primary aim was to provide a comprehensive characterization of depressive symptom profiles in a national sample of healthy adults. Investigators identified empirically derived depressive symptom profiles based on continuous measures of negative affect, loss of interest, somatic complaints, sleep disturbances, interpersonal difficulties, and positive affect. Indicators used in these analyses to characterize symptom profiles included: (1) the MASQ Depressive Symptom subscale, (2) the MASQ Loss of Interest subscale, (3) the MASQ Positive Affect subscale, (4) the CES-D Negative Affect subscale, (5) the CES-D Somatic Features subscale, (6) the CES-D Interpersonal Disturbance subscale, and (7) the PSQI Global Score.

Based on the presentation and severity of symptoms, 4 latent depressive symptom profiles were identified and labeled as follows:

  • No symptoms
  • Mild symptoms
  • Moderate symptoms
  • Acute symptoms

Logistic regression models were used to describe the relationship between these subgroups and cardiometabolic outcomes, including metabolic syndrome and obesity, with the following results:

  • The moderate symptoms subgroup was significantly associated with metabolic syndrome.
  • Both the mild symptoms (trend) and moderate symptoms subgroups were associated with obesity after controlling for demographic factors, anti-depressant use, presence of chronic conditions, and health behaviors.
  • Inflammation attenuated the association between these subgroups and cardiometabolic outcomes, suggesting that inflammation may be a biological mediator linking symptom profiles and cardiometabolic outcomes.

The authors concluded by noting the novelty of these findings, also indicating that future work should examine differential pathways to increased risk across depressive symptom profiles and examine whether tailored interventions have an impact on cardiometabolic risk.

References

Chirinos DA, Murdock KW, LeRoy AS, et al. Depressive symptom profiles, cardio-metabolic risk and inflammation: results from the MIDUS study. Psychoneuroendocrinology. 2017;82:17-25.

Del Grande da Silva G, Wiener CD, Barbosa LP, et al. Pro-inflammatory cytokines and psychotherapy in depression: results from a randomized clinical trial. J Psychiatr Res. 2016;75:57-64.

Pan A, Keum N, Okereke OI, et al. Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care. 2012;35:1171-1180.

Shelton RC, Miller AH. Eating ourselves to death (and despair): the contribution of adiposity and inflammation to depression. Prog Neurobiol. 2010;91:275-299.

Womack, VY, De Chavez PJ, Albrecht SS, et al. A longitudinal relationship between depressive symptoms and development of metabolic syndrome: the coronary artery risk development in young adults study. Psychosomatic Med. 2016;78:867-873.

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